N-hydroxycarbanilidies and their use as bactericides and fungicides



United States latent O ice.

3,189,645 N-HYDROXYCARBANILIDES AND THEIR USE AS BACTERICIDES ANDFUNGICIDES Peggy Pamela Hoffman, Somerviiie, and Wiiliam Baptist Hardy,Bound Brook, N.J., assignors to American Cyanamid Company, New York,N.Y., a corporation of Maine No Drawing. Filed Aug. 8, 1961, Ser. No.129,999 4 Claims. (6]. 269-553) This invention relates to new germicidesand to detergent compositions containing these germicides. Morespecifically this invention relates to N-hydroxycarbanilides having atleast two substituents of the group consisting of halogen andtrihalomethyl, and which may be further substituted by halogen, nitro,lower alkyl or lower alkoxy radicals; and to non-ionic and anionicdetergent compositions containing them.

In recent years, increased attention has been given to the developmentof textile purifying finishes. These finishes inhibit the growth, andreduce the number of microorganisms on the material. These purifyingfinishes, when applied to articles of clothing worn close to the body,are also helpful in preventing the development of body odors.

A satisfactory purifying finish should be durable and active at lowconcentrations against a broad spectrum of microorganisms. It should benon-toxic and nonallergenic. It should not have the tendency tosensitize the wearer of the textile fabric to the material of thefinish. It should not have the property of allowing strains of bacteriato develop which are resistant to the antibacterial agent of the finish.It should impart little or no color to the fabric and should be stablewith respect to color and activity for many months under storage andshipping conditions. It should be resistant to the conditions used inlaundering and dry cleaning. It should cause little or no modificationof the hand of the textile. It should be substantive to the fiber. Itshould be compatible with dyes and resins with which it may be incontact on the textile. 1

Various textile purifying finishes containing anti-bacterial substancessuch as hexachlorophene, tetrachlorophene, quaternary ammonium compoundssuch as dimethyl benzyl ammonium chloride, organo-metallic complexes ofmercury, copper and silver, and others have been used but are for themost part non-durable and unsatisfactory in other respects, especiallyin their inability to exhaust from a laundry bath.

substantivity on the fiber and durability of the antibacterial actionare two of the most important desirable properties. Withoutsubstantivity on the fiber the germicide is merely a coating to berubbed or washed oif by the first treatment to which it is subjected.substantivity for the fiber is, therefore, one of the main bases uponwhich durability rests. However, durability must also be a function ofthe stability of the compound itself to oxidation by air, degradation bylight, heat and the like.

Especially important is the property of substantivity under launderingconditions and especially of exhaustion from such a laundry bath in thesame way that a dye exhausts from a dye bath. If a germicide is to havethe widest utility as a textile finish, the best place to use it is inthe regular laundering, whether in the home or in a hospital or acommercial laundry. Such a germicidal finish builds up in concentrationon the fiber with further Washing since new applications of germicideare made during such further washing.

This invention is based on the discovery of a new class of compounds,defined above, the members of which have high germicidal action and aresubstantive to fabrics. The

Fa -tented June 1 5, T955 new compounds may be represented by thestructural Formula 1:

wherein the X X X X X Y Y Y Y and Y are individually either hydrogen,halogen (especially chlorine and bromine), nitro, lower alkyl, lower.alkoxy and trihalomethyl (e.g. trichloromethyl and especiallytrifluoromethyl), at least two of the X and Y radicals being halogen ortrihalornethyl. Within the class of compounds constituting thisinvention those compounds which have halo and/ or trihalomethyl groupsin both phenyl moieties are preferred since they generally show greatergermicidal activity than the analogs which are substituted in only onephenyl moiety. It has also been found that those compounds having atleast one 3,4-dichlorophenyl radical, 3,4,5-trichlorophenyl radical, andparticularly a 3,5-dichlorophenyl radical or a S-trifluoromethylphenylradical show higher activity than those in which the chloro radicals arein the 2- or the 6-positions of the phenyl moieties.

The new compounds of this invention may be prepared by reacting a phenylisocyanate with an N-phenylhydroxylamine in the presence of a non-polarhalogenated organic solvent (e.g. chloroform) or an aromatic monocyclichydrocarbon (e.g. benzene, toluene and xylene) at ambient temperaturesusing approximately equimolar proportions of the reactants. The reactionmay be represented by the following equation in which X X X X X Y Y Y Yand Y are as hereinbefore defined.

I I I I X -QNCO norm-@414 I I I X5 X5 Ya Ya X3 X2 Y2 Y3 I I I I I 0 X5 iI I As examples of suitable phenyl isocyanates which may be used, thesemay be named inter alia: phenyl isocyanate, 2-, 3- and 4-chlorophenylisocyanate, 2,3, 25-, 3,4- and 3,5-dichlorophenyl isocyanate,3-(trifiuoromethyl)phenyl isocyanate and 3,5-bis(trifluoromethyl)phenylisocyanate, 2-, 3- and 4-bromophenyl isocyanate, 3,4 and3,5-dioromophenyl isocyanate, 3,4,5-trichlorophenyl isocyanate, 3- and4-nitrophenyl isocyanate, 2-, 3- and 4-methylphenyl isocyanate,3-(trifiuoromethyl) 4 bromophenyl isocyanate,3-(trifiuoromethyl)-4-chlorophenyl isocyanate and 4-methoxyphenylisocyanate.

As examples of suitable N-phenylhydroxylamines which may be used, thesemay be named inter alia: N-phenylhydroxylamine,N-(Z-chlorophenyl)hydroxylamine, N-(4- chlorophenyl)hydroxylamine,N-(3-chlorophenyl)hydroxylamine, N- (4-iodophenyl) hydroxylamine, N-(2,5 -dichlorophenyl)hydroxylamine, N-(3,4-dichlorophenyl)hydroxylamine,N 3,5 dichlorophenyl)hydroxylamine, N 3- (trifiuoromethyDphenylhydroxylamine, N-3 (trichloromethyl) phenyl hydroxylamine,N-(3,4,5-trichlorophenyl) hydroxylarnine, N-(2-methyl 3chlorophenyl)hydroxylamine, N- Z-methyl-S-chlorophenyl) hydroxylarnine,and N 2-methyl-4,S-dichlorophenyl hydroxylamine.

The germicides of this invention when padded or exhaust dyed on cloth,show such germicidal activity that Staphylococcus aureus and E. cell,for example, are inhibited not only where in contact with the treatedcloth, but in an area beyond. After many Washing cycles, the

a padded fabric still shows activity against Staphylococcus aureus andE. coli in contact with the cloth.

It is an important advantage of the germicides of this invention thatthey become attached to fibers when applied from an aqueous bath at onlyslightly elevated temperatures. They have notably strong afiinity forcotton and may be applied to cotton in temperatures as low as those usedin laundry procedures. They may also be applied at.th e highertemperatures normally used in the dyeing of cotton, i.e. near the boil.These compounds are thus particularly suitable for hospital and homeuse, where it is more difficult to attain the temperatures close to theboil that are used in a dyeing mill. In addition to cotton, thegermicides of this invention have afiinity for other fibers such asnylon, cellulose acetate and the like when applied from laundry bath. 7

The compounds of this invention are compatible with non-ionic andanionic detergents. This is a further :advantage of this invention sincethe germicide can be ap-1 plied from a detergent bath such'as is used inlaundering in the home or in a hospital. Germicidal compositionsincluding the compounds of this invention in admixture with alkyl arylsulfonates (anionic detergents) are espe cially suitable compositionsfor the application for'durable finishes to cotton and other fibersespecially during home or commercial laundering procedures. During theprocess of laundering, the germicide becomes attached to'the fiber andthe fiber is thusrendered sterile for long periods. A detergentcomposition having from about 0.01 to 5.0% germicide on the weight ofthe detergent is an effective composition for this purpose.

The organic anionic detergents which may be used in the'compositions ofthis invention include alkali metal fatty acid soaps and, in addition,the well known surfaceactive alkali metal sulfonates and sulfates. Thelatter may be employed as the sole detergent base or in admixture withalkali metal fatty acid soaps, as for example, 1 part of fatty acid soapto 0.5 to '2 parts by weight of the surface-active alkali metalsulfonates or sulfates or mixtures thereof. A preferred group of thisclass is the long chain alkyl aryl sulfonates, i.e., those wherein thealkyl group is straight or branched in structure and contains from 8 to22 carbon atoms, but preferably 10 to 16 carbon atoms, examples of whichbeing octyl, decyl, dodecyl, pentadecyl, hexadecyl, octadecyl, mixedlong chain alkyl' derived from long chain fatty acids such as the laurylradical, cracked parrafin wax olefins, polymers of low mono-olefins suchas propylene tetramer and the like, and wherein the aryl radical isderived from benzene, toluene, xylene, phenol, the cresols, naphthaleneand the like. Specific examples of such comprise sodiumdecylbenzenesulfonate, sodium dodecylbenzenesulfonate,

sodium laurylbenzenesulfonate, and sodium hexadecylbenzenesulfonate.Other sulfonate surface active agents are contemplated also, as forexample, the long chain :alkyl sulfonates such as sodium hexadecylsulfonate and .and mixed alkyl sulfates, and higher sulfates such assodium lauryl sulfate and sodium cetyl sulfate.

Additional .anionic surface active sulfonates and sulfates contemplatedby this invention are the sulfonated and sulfated'alkyl acid amides suchas Igepon T of the formula C H CONHCH CH SO N21 The sulfated andsulfonated esters such as Igepon AT of the formula Such detergentsinclude sulfuric acid esters of din which R is an alkyl radicalcontaining from 12-18 carbon atoms, the sodium salt of the sulfonic acidderivative of a dialkyl dicarboxylate, disodium sulfosuccinate monoamidesuch as and the like. ,j In addition to the. anionic surface activeagents, nonionic surface active agents may be used as the base forgermicidal compositions of our invention. Thenon-ionic surface activeagents which may be used are viscous liquid, wax-like, water solublesurface active substances containing a polyglycol ether group of thestrucmre Z1 Z2 in which Z and Z are hydrogen or a short chain alkyl,

p is an integer greater than three and Z is a residue of V typified bypolyalkylene oxide derivatives (e.g. polyethylene oxide, polypropyleneoxide, polybutylene oxide) of water-insoluble higher fatty acids, suchas lauric, 'oleic, palmitic and stearic and the like, or'mixturesthereof such as the mixtures of fatty acids obtained from animal andvegetable fats and oils and by the oxidation of petroleum fractions suchas parafin wax; They may also be exemplified by the polyalkylene oxidederivatives of such water-insoluble organic hydroxy compounds as higheraliphatic compounds (i.e. the alcohols corresponding to the fatty acidsspecified above or mixtures thereof) phenols, particularly alkyl phenolscontaining at.least six alkyl carbon atoms such as isooctyl,triisopropyl, nonyl, dodecyl, octadecyl phenols or naphthols, or ofaralkyl alcohols such as benzyl alcohol, cinnamyl alcohol and the like.They may also be exemplified by the polyalkylene oxide derivatives ofsuch amines as 'stearyl, lauryl, dicyclohexyl, dibutyl amine and thelike. ticularly useful non-ionic detergent is that obtained bycondensing one mole of tall oil with 5-15 moles of' Staphylococcusaureus, that they are effective against the other gram positive bacteriawhich break down perspiration into odoriferous products.

The germicides .of this invention may also be applied 7 to surfaces.This'can be done in the form of a solution in dimtehylformamidecontaining 0.01 to 1.0% on the Weight of the germicide. In addition,more concentrated solutions may be added to cleaning materials, floorwaxes and the like to give a final concentration of 0.01 to 1.0%

germicide for application to a surface. Such an application produces asurface which is durably germicidali This invention can be illustratedby the following examples in which parts are by weight unless otherwisespecified.

' EXAMPLE 1 3,3-dich[oro-N-hydroxycarbanilide To a solution of 3.59parts' of N-(3-chlorophenyD- hydroxylamine in parts of chloroform areadded 3.84 parts of 3-chlorophenyl isocyanate. is stirred for two hoursat room temperature and their the precipitate is filtered off. Afterdrying in vacuo, the; product is purified by crystallization fromaqueous metharsuil. The almost white crystals melt at about 150 1 C. e r

These non-ionic detergents are well known 7 {c.g. US. 1,970,578 and US.2,213,477) and may be A par- Thefresulting slurry" This compound showsmore than .a three fold increase in activity by standard agar dilutionprocedures as compared with the non-N-hydroxylated analog, againstStaph. aureus. It shows a correspondingly greater activity when paddedfrom a dimethylformamide solution onto cotton against Staph. aureus andE. coli.

EXAMPLE 2 3',5'-dichloro-N-hydroxycarbanilide A solution of 9.40 g. of3,5-dichlorophenyl isocyanate in 150 parts of chloroform is added to asolution of 5.46 parts of N-phenylhydroxylamine in 300 parts ofchloroform. The resulting slurry is stirred at room temperature for twohours. The precipitate is filtered ofi, dried at room temperature andrecrystallized from benzene to give a white product melting at aboutl51-152 C.

EXAMPLE 3 3-triflu0r0methyl- ',4'-dichl0r0N-hydroxycarbanilide C Fe To asolution of 14.23 parts of 3-(trifluoromethyl)- nitrobenzene in 65 partsof ethanol is added a solution of 1.6 parts of ammonium chloride inparts of water. While stirring at the reflux temperature, zinc dust isslowly added (about 28 parts) until the reaction mixture becomescolorless. After the reaction mixture has been cooled and the reactionvessel flushed with nitrogen, 90 parts of benzene are added, and thereaction mixture is well stirred. The benzene containing the reactionproduct, namely N-[3-(trifiuoromethyD-phenyl]hydroxylamine, is separatedand dried with anhydrous sodium sulfate.

The above solution of N-[3-(trifluoromethyl)-phenyl] hydroxylamine inbenzene is added to a solution of 6.6 parts of 3,4 dichlorophenylisocyanate in parts of benzene. After stirring at room temperature fortwo hours, the benzene is removed by distillation in vacuo. The residueis slurried with chloroform and filtered to obtain the product which,after crystallization from aqueous methanol, appears as almost whitecrystals melting at about 148-l49 C.

The product shows high activity against Staph. aureas and E. coli whenpadded onto cotton (1% on the weight of the fabric) from a solution indimethylformamide (DMF). The non-hydroxylated analog shows nosigriificant activity under the same conditions.

EXAMPLE 4 3,3',4,4 tetrachloro-N-hydroxycarbonilide The solution ofN-(3,4-dichlorophenyl)hydroxylamine in benzene is added to a solution of8.45 parts of 3,4- dichlorophenyl isocyanate in 40 parts of benzene.After stirring the reaction mixture at room temperature for two hours,the benzene is removed under vacuo and the a residue slurried withchloroform. The product obtained by filtration, and recrystallized fromaqueous methanol, melts at about -141 C. with decomposition.

The above product prepared by the procedure of Ex ample 4 using thecorresponding phenyl isocyanate and N-phenylhydr oxylamine and whentested by the conventional agar dilution method against Staph. aurea'sshows more than seven times the activity of the non-hydroxylatedderivative tested by the same method.

Example 6 The above product prepared by the procedure of Example 2 usingthe corresponding phenyl isocyanate and N-phenylhydroxylarnine and whentested by the conventional agar dilution method against Staph. aureusshows more than four times the activity of the non-hydroxylatedderivative tested by the same method.

EXAMPLE 7 C F Cl I on Fab (a non-ionic detergent) on the weight of thefabric.

This compound is extremely active against S. aureas in the agar dilutiontest.

EXAMPLE 8 This product prepared by the reaction of 3-chlorophenylisocyanate and N-(3,5 dichlorophenyl)hydroxylamine, prepared from3,5-dichloronitrobenzene under the conditions of Example 4, having amelting point of about 179 C. when padded onto cotton (1% on the weightof the fabric) from a solution in DMF shows good activity against E.coli as compared to the non-N-hydroxylated analog which has negligibleactivity under the same conditions.

This product prepared by the reaction of p-chlorophenyl isocyanate andN-(3,4,5-trichlorophenyl)hydroxylamine, prepared from3,4,5-trichloronitrobenzene under the conditions of Example 4, having amelting point of 198 C. shows good activity against Staph. am'eus in the'agar dilution method and against Staph. aureus and E.

coli when applied to cotton by both the padding and exhaustionprocedures as described hereinbefore.

EXAMPLE 10 This product prepared by the reaction of 3,4-dich1orophenylisocyanate and N-'(p-chlorophenyl)hydroxylamine by the reaction shown inExample 2 has a melting point of about 150-151 C. and is active againstStaph. aureus and E. coli when applied to textiles and against Staph.aureus in the agar dilution test.

EXAMPLE 11 C1 G1 (1711 I This product prepared by the reaction of3,5-dichlorophenyl isocyanate and N-(3,5-dich1orophenyl)hydroxylaminehaving a melting point of 184 C. is highly active against Staph. aureusand E. coli.

EXAMPLE 12 EXAMPLE 13 7 0 H -r Q C1 This compound prepared by thereaction of S-(trifluorornethyDphenyl isocyanate withN-(p-chloropheny1)- hydroxylamine under the conditions of Example 2having a melting point of about 125 C. when padded onto cotton (1% onthe weight of the fabric) from a solution in DMF shows high activityagainst Staph. aureus as compared to the corresponding non-hydroxylatedcompound whichv shows a negligible activity under the same conditions.

EXAMPLE 14 C1 G1 I I V V A ,7 I 7 C1 Cl This product prepared by thereaction of 3,4,5-trich1orophenyl isocyanate withN-(3,4,5-trichlorophenyl)hydroxylamine prepared from3,4,S-trichloronitrobenzene underthe conditions of Example 4, having amelting'point of about ZOO-210 C. is active against Staph. aureus whenexhaust dyed onto cottonfrom both 0.1% and O.5% (on 8 weight of thefabric) aqueous solutions containing a nonionic detergent.

1 EXAMPLE 15 I .i 0 V V 01 This product prepared by the reaction of3,4,5-trichlorophenyl isocyanate andN-[3-(trifiuoromethyl)phenyl]hydroxylamine, prepared from3-(trifluoromethyl)nitrobenzene under the reaction conditions of Example4, having a melting point of about 170172 C. shows good activity againstStaph. aureus. 7'

EXAMPLE 16 I OH This product prepared by the reaction of p-bromophenylisocyanate with N- (3,5-dich 1orophenyl)hydroxylamine, preparedfrom3,5-dichloronitrobenzene under the conditions of Example 4, having amelting point of 18ll82 7 C. is activeagainst Staph. aureau and E. coliin the cotton padding test hereinbefore described.

EXAMPLE 17 This product prepared by the reaction of 3-nitrophenyl Visocyanate and N (3 ,5 -dichlorophenyl) hydroxylamine,

' prepared from 3,5-dichloronitrobenzene underthe reaction conditions ofExample4, having a melting point of about 189 C. shows activity. againstStaph. aureus and E. coli when padded onto cotton fabric (1% on the.

weight of the fabric) from a-solution in DMF.

A corresponding p-nitro isomer having a melting point of l82l83 C. ishighly active against Stap' h. aureus in the agar dilution test. 7

EXAMPLE 18 Cl OH This product prepared by the reaction ofp-methoxyphenyl isocyanate and N-(3,5-dichlorophenyl)hydroxylamine,prepared from 3,5-dichloronitrobenzene by the procedure of Example 4,having a melting point of 170 171 C. is active against Staphaureus inthe cotton padding test.

The product prepared from the corresponding p-methylphenyl isocyanatehaving a melting point of C. is

likewise an active germicide under the same test conditions.

EXAMPLE 19 0 F3 7 01 I (1311 l The carbanilide of the above formula from3-(trifiuoromethyl)-4-bromophenyl isocyanate andN(3,4-dichlorophenyl)hydroxylamiue prepared from3,4-dich1oronitrobenzene by the procedure of Example 4, having a meltingpoint of about 167 C. shows greater activity than the correspondingnon-hydroxylated analog against Staph. aureus when padded onto thefabric.

EXAMPLE 20 C F 3 C I I (l) H i Q I O C F a C1 This product prepared bythe reaction of 3,5-bis(trifiuoromethyl)phenyl isocyanate andN-(3,5-dichlorophenyhhydroxylamine prepared from3,5-dich1oronitrobenzene under the reaction conditions of Example 4,having a melting point of about 188-189 C. shows more than a 15 foldincrease in activity against StapIh. aureus in the agar dilution test ascompared to the corresponding nonhydroxylated analog.

EXAMPLE 21 This product obtained by the reaction of3-(trifluoromethyl)-4-chlorophenyl isocyanate withN-[3-(trifluoromethyl)phenylJhydroxylamine prepared from3-(trifluoromethy1)nitrobenzene by the reaction of Example 4, having amelting point of 147148 C. shows good activity against Staph. aureus andE. 0012' when padded onto cotton fabric (1% on the weight of the fabric)from a solution in DMF.

EXAMPLE 22 This product obtained by the reaction of3-(trifluoromethyl)-4-chlorophenyl isocyanate withN-(3,4-dichloropheny1)hydroxylamine, prepared from3,4-dichloronitrobenzene by the reaction in Example 4, having a meltingpoint of 161162 C. shows very good activity against E. coli when paddedon cotton fabric as compared with negligible activity by thecorresponding compound without the hydroxyl group.

EXAMPLE 23 C F; G1

This product obtained by the reaction of3-(trifluoromethyD-4-bromophenyl isocyan-ate withN-(3,4,5-trichlorophenyl)hydroxylamine, prepared from3,4,5-trichloronitrobenzene by the reaction of Example 4, having amelting point of C. shows excellent activity in agar against Staph.aureus.

EXAMPLE 25 I OH HQ This product obtained by the reaction of2,3-dichl'orophenyl isocyana-te with N(3-chlorophenyl)hydroxylamineunderthe reaction conditions of Example 2 having a melting point ofl61l62 C. is active against Staph. aureus when padded on cotton and inthe agar dilution test as compared with insignificant activity againstStaph. aureus of the non-hydroxylated analog.

EXAMPLE 26 C1 C1 I I This derivative obtained by the reaction of2,5-dichlorophenyl isocyanate with N-(3-chl-orophenyl)hydroxylamine,having amelting point of 158-159 0., as compared with thenon-hydroxylated analog shows good activity in the agar dilution testand when padded onto cotton fabric.

EXAMPLE 27 Cl OH:

I OH

This derivative obtained by the reaction under the conditions of Example2 of 3,4-dichlorophenyl isocyanate withN-(2-methyl-3-chlorophenyl)hydroxylamine having a melting point of 179C. shows good activity against Staph. aureus when padded :onto cottonfabric.

EXAMPLE 28 or 0 r (Ina !T his derivative prepared by the reaction ofZ-(trifiuoromethyl)phenyl isocyanate with N-[3-(-trifiuoromethyl)-phenylJhydroxylamine prepared from 3-(trifluoromethyl) nitrobenzene bythe procedure of Example 4, having a melting point of about 127 C. showsvery good activity against E. coli when padded on cotton as compared toinsignificant activity of non-hydroxylated analog. It also shows threetimes the activity of the non-hydroxylated derivative in the agardilution test against Staph. aureus.

The product obtained by the reaction of 3,5-dichlorophenyl isocyanatewith N-(4-iodop-henyl)hydroxylamine under the reaction conditions ofExample 2 is active against Staph. aureus.

EXAMPLE 30 CCIa The product obtained by the reaction of 3,5-dichlorophenyl isocyan-ate with N-[3-(trichloromethy1)phenyl]- 1 1 hydroxy-lamine by the reaction conditions of Example 4 is active againstStaph. aureus.

EXAMPLE 31 Cl 7 Cl This derivative obtained by the reaction of3,4-dichlorophenyl isocyanate with N-(3,5-diohlorophenyl)hydroxyl-"amine, prepared'from 3,5-dich1oronitrobenzene under the conditions ofExample 4, shows good activity against Staph. aurezis when padded oncotton fabric.

EXAMPLE 32 This derivative obtained by the reaction of3,4,5-trichlorophenyl isocyanate with N-(3,5-dichlorophenyl)-'hydroXyla-mine, prepared from 3,5-dichloronitrobenzene under theconditions of Example 4, shows excellent activity against Staph. aureusin the agar dilution test.

EXAMPLE 3 3 F 3 C l I O H -Q This derivative obtained by the reactionof3-(trifiuoromethyDphenyl :isocyanate with N-(-3,5-dich1oropheny1)-hydroxylam-ine, prepared from 3,5-dich1oronitrobenzene under theconditions of Example 4, shows very good activity against Staph. aureuswhen padded on cotton fabric.

We claim: V

' 1. An N-hydroxy carbanilide wherein the non-hy- V droxylated nitrogenatom is unsubstituted and the phenyl moieties of the carbanilide aresubstituted by m halo and n trihalomethyl groups wherein m is an integerless than eleven and n is an integer less than five and 1 2 the total ofm than eleven wherein the halo groups have an atomic number less than 54and the remaining valences of the phenyl moieties are satisfied bymembers selected from the group consisting of hydrogen, nit-r0,- loweralkyl and lower alkoxy.

2. The compound of the formula 3. The compound of the formula Cl 7 01 II H 4. The compound of the vformula GFs C1 References Cited by theExaminer UNITED STATES PATENTS OTHER REFERENCES 7 Seheiber: J. Prakt.Chem., vol. 78, (1909), pages 74- 9.

NICHOLAS s. RIZZO, Primary Examiner. J. GREENWALD, WALTER A. MODANCE,Examiners,

and n is greater than one and less UNITED STATES PATENT OFFICECERTIFICATE OF CORRECTION Patent No. 3,189,645 June 15, 1D65 PeggyPamela Hoffman et al.

It is hereby certified that error appears in the above numbered patentrequiring correction and that the said Letters Patent should read ascorrected below.

Column 4, line 52, for "dimtehylformamide" read dimethylformamide column8, line 27, for "aureau", in italics, read aureus in italics; column 9llnes 50 to 55, the formula should appear as shown below instead of asin the patent:

(1P im 1 BTQNH-fi-N same column 9,

lines 66 to 71, shown below ins the formula should appear as tead of asin th e patent:

CB5 w 1 OH BrQNII-fl-IL c1 column 10, lines 30 to 35,

the formula should appear as shown below instead of as in the patent:

column 12, lines 8 to 14, the formula should appear as shown belowinstead of as in the patent:

same column 12, lines 15 to 20, the formula should appear as shown belowinstead of as in the patent:

Signed and sealed this 16th day of November 1965.

(SEAL) attest:

ERNEST W. SWIDER EDWARD J. BRENNER Attesting Officer Commissioner ofPatents

1. AN N-HYDROXY CARBANILIDE WHEREIN THE NON-HYDROXYLATED NITROGEN ATOMIS UNSUBSTITUTED AND THE PHENYL MOIETIES OF THE CARBANILIDE ARESUBSTITUTED BY "M" HALO AND "N" TRIHALOMETHYL GROUPS WHEREIN "M" IS ANINTEGER LESS THAN ELEVEN AND "N" IS AN INTEGER LESS THAN FIVE AND THETOTAL OF "M" AND "N" IS GREATER THAN ONE AND LESS THAN ELEVEN WHEREINTHE HALO GROUPS HAVE AN ATOMIC NUMBER LESS THAN 54 AND THE REMAININGVALENCES OF THE PHENYL MOIETIES ARE SATISFIED BY MEMBERS SELECTED FROMTHE GROUP CONSISTING OF HYDROGEN, NITRO, LOWER ALKYL AND LOWER ALKOXY.